Real-world effectiveness and safety of ofatumumab in relapsing multiple sclerosis: A multicenter cohort study

To evaluate the real-world effectiveness, safety, and tolerability of ofatumumab in people with relapsing multiple sclerosis (pwMS) in Croatia.

We conducted a retrospective observational study in eight Croatian hospitals (March 2022-March 2025). Clinical, MRI, and laboratory data were collected before treatment initiation and every six months. Effectiveness measures included annualized relapse rate (ARR), MRI activity, and sustained accumulation of disability (SAD), and the proportion achieving no evidence of disease activity (NEDA-3). Safety assessments included adverse events (AEs), immunoglobulin levels, infections, and pregnancy outcomes.

The study included 665 pwMS (65.6 % female; mean age 40.2 ± 10.7 years; 59.7 % treatment-naïve). Median follow-up was 1.55 years. ARR decreased from 0.70 ± 0.67 pre-treatment to 0.03 ± 0.18 post-treatment (p < 0.001). MRI activity occurred in 17.1 % of patients; 76.7 % achieved NEDA-3. SAD was observed in 6.3 % of pwMS, with male sex as the only independent predictor. Ofatumumab discontinuation occurred in 4.2 % of patients, mainly due to pregnancy. Injection reactions occurred in 15.8 % and infections in 7.4 % (3 hospitalizations). IgG and IgM declined slightly over time, with low IgM (<0.4 g/L) persisting in >10 % after two years, but without correlation to infection rates. Two malignancies were observed. Pregnancy outcomes were favorable in most cases.

In a real-world Croatian cohort, ofatumumab demonstrated high effectiveness in reducing relapses and MRI activity, with a favorable safety profile over three years. These findings align with pivotal trial results, supporting ofatumumab as an effective and well-tolerated therapy for active relapsing MS in clinical practice.